Wiring the Brain, Literally, to Treat Stubborn Disorders

By

Melinda Beck

January 17, 2012

The procedure starts with a surgeon drilling two holes in the patient's skull. "Every bone and tooth in my head was rattling," says Lisa Battiloro, who was awake, but not in pain, during the eight-hour operation.

Neurologists asked her questions and issued commands as they pinpointed the exact spot in her brain for electrical stimulation. At one point, "I suddenly felt hopeful and optimistic about the future," recalls Ms. Battiloro, who had battled severe depression for more than a decade. That's when the doctors knew they had found Brodmann 25, an area deep in the cerebral cortex associated with negative mood. They secured the electrodes in place, then sedated Ms. Battiloro while they ran an extension wire under the skin, down the side of her head and into her chest, where they implanted a battery pack to supply her brain with a mild electrical current.

Powerful Electrodes

Researchers think deep brain stimulation could help with a wide range of disorders:

Within two months, Ms. Battiloro says, her depression had lifted considerably. Now, nearly four years later, it hasn't returned. "My friends and family are amazed," say Ms. Battiloro, 41, of Boynton Beach, Fla. "I'm a new and improved Lisa."

Deep brain stimulation, sometimes called a pacemaker for the brain, has helped halt tremors in more than 100,000 patients with Parkinson's disease and other movement disorders since 1997. Now, researchers are reporting encouraging results using the procedure for psychiatric conditions as well. Ms. Battiloro was one of 17 patients in a study published this month in the Archives of General Psychiatry. After two years of DBS, 92% reported significant relief from their major depression or bipolar disorder and more than half were in remission, with no manic side effects.

"We are seeing dramatic effects in the small numbers of subjects, and they are not just getting well, they are getting well without side effects and without relapsing," says neurologist
Helen Mayberg,
who led the study at Emory University in Atlanta.

Other clinical trials are studying DBS as a treatment for epilepsy and obsessive-compulsive disorder; some researchers are experimenting with it for Alzheimer's disease, tinnitus, addiction and Tourette syndrome, a condition that causes sudden movements and tics. But such uses could be many years away. "DBS is a potential treatment for any condition where you have a good idea which brain regions aren't functioning appropriately," says
Paul Holtzheimer,
director of the Mood Disorders Service at Dartmouth-Hitchcock Medical Center, who collaborated on the study while at Emory. "But you need to do the clinical trials and have good evidence of the safety and efficiency to balance the invasiveness of the surgery."

Deep brain stimulation has helped halt tremors in more than 100,000 patients with Parkinson's disease and other movement disorders. Now, researchers are using the procedure for psychiatric conditions as well. Melinda Beck has details on Lunch Break.

Neurologists don't know exactly how DBS improves brain function. But there is growing recognition that the brain operates via complex electrical circuits that sometimes malfunction, and that electrical stimulation can interrupt the errant signals. Years ago, scientists noticed that Parkinson's disease involved excess activity in the brain's subthalamic nucleus—a spot about the size of a pea in the basal ganglia. In essential tremor, an even more common disorder with involuntary shaking, the target is the ventrointermediate nucleus, just a few millimeters away.

Pinpointing depression in the brain has been trickier, since it involves multiple brain circuits that control mood, thought, sleep, reward and other functions. Dr. Mayberg's team spent years scanning the brains of depressed patients and noticed that many who got better had changes in Brodmann Area 25, whether they were treated with medication, psychotherapy or electroconvulsive therapy. Other researchers are targeting different spots in the brain that may play a role in depression. Larger clinical trials are under way, but Food and Drug Administration approval of DBS for depression is still several years away.

In movement disorders, the results can be dramatic—even in the operating room when the electrodes are first tested. "They say, 'Hold up your hands and all of a sudden, there is no tremor!" says Pamela Bland, a former nurse from Dunnellon, Fla., who was diagnosed with Parkinson's in 2000 and couldn't walk, talk or get out of bed at the time she had the surgery at the University of Florida in Gainesville in 2008. Now she drives, kayaks and even completed a recent 5-K race. "There's not much I can't do," says Ms. Bland, now 62.

ENLARGE

Mike Sudal/The Wall Street Journal

It can take months to fine-tune settings on the battery pack and adjust medications to give patients optimal movement control. But in rare cases, the surgery alone seems to reset the brain circuits. Tom Rogers, a former truck driver who could no longer drive, write or drink from a glass due to severe tremor, had the electrodes implanted last summer and his shaking stopped immediately—even though the electricity has never been turned on. "My hand is steady as a rock," marvels the 66-year-old Oswego, Ill., resident.

Researchers think the same phenomenon may explain why patients in the control groups of some DBS trials have improved after their electrodes were implanted but before the current was turned on.

That control benefit was also seen in a study published in the journal Lancet Neurology last week. Some 136 Parkinson's patients in 15 centers in the U.S. received a DBS system made by St. Jude Medical Inc., which is hoping to win FDA approval to market it in the U.S. In half the patients, the devices weren't turned on for three months to serve as a control group. Nearly 40% of the control subjects reported gaining at least two more hours of good movement control per day, compared with 73% of the group undergoing active stimulation. On average, those with the active devices increased their hours of good movement control from 6.3 hours to 11 hours per day. As of now, Medtronic Inc. makes the only DBS devices approved for sale in the U.S.

Only 10% to 15% of Parkinson's patients are good candidates for DBS, says
Michael Okun,
medical director of the National Parkinson Foundation. It's most useful for people experiencing tremor, stiffness and other movement problems but not other cognitive problems or health issues. DBS isn't a cure for Parkinson's; the disease still progresses. And as with other surgeries, there is a risk of infection, stroke or other complications. Some patients find their speech slurred after the surgery, and others report falling issues.

Still, demand for DBS is rising steadily. "In the beginning, it was tough to get patients onto the table. Now it's the opposite," says Dr. Okun, who performs many DBS operations a year at the University of Florida's Center for Movement Disorders. The procedure, which costs about $60,000 including hospital fees, is generally covered by Medicare and private insurers for Parkinson's, essential tremor and dystonia, another movement disorder.

Although some neurologists are offering DBS for depression even before it wins FDA approval, experts urge people with severe, treatment-resistant depression who are interested in DBS to enroll in a clinical trial, where they can be carefully monitored.

PROFILES OF DBS PATIENTS

ENLARGE

Lisa Battiloro
Battiloro family

Lisa Battiloro was diagnosed with major depressive disorder at age 22 in 1992 and began a frustrating treatment odyssey. "I tried many pharmaceuticals," she says. "I tried cognitive-behavior therapy. I had 122 shock treatments. At first they helped, but they started to help less and less. I also had TMS (transcranial magnetic stimulation, another form of electrically recharging the brain.) I got no response to that at all."

Her physician knew of Helen Mayberg's work at Emory University. Ms. Battiloro went for an interview, applied, was accepted and was one of the first 17 patients in 2008. She was determined not to get her hopes up. "I was thinking, 'If this treatment doesn't work, there's always suicide,' " she recalls.

She felt somewhat better immediately after the surgery—even though she now knows she was part of a control group whose devices weren't turned on for another month. After the second month (with the current active), "It was a consistent climb. I was sleeping better. I wasn't binge eating. I didn't have any suicidal thoughts." Ms. Battiloro has now renewed her nursing license and hopes to resume her career.

She can't go through airport scanners or have an MRI, and she does have a scar on her chest where the battery pack is implanted. "That's my badge of courage," she says. "But I don't have that feeling of dread, that numbness anymore. It's been consistent and stable. I still have the occasional off day, but everybody does, and now I'm able to get up and get on with my life."

* * *

Matthew Miller was 8 years old when his hands started shaking. It went away in his teenage years but returned in his 20s, when he was diagnosed with essential tremor, a movement disorder that is 10 times more common than Parkinson's disease and often runs in families. Medications can control it temporarily, but Mr. Miller built up a tolerance to each one and he was exhausted trying to sit still and work at a computer.

"It was even difficult socially—you don't dare go to a restaurant because your food will fly everywhere," he says.

Mr. Miller was the first patient to be treated with Deep Brain Stimulation for essential tremor at Swedish Medical Center in Seattle in 2005. The operation, since streamlined, took 12 hours. In tremor patients, the surgeons listen for a specific kind of static on a Geiger-counter like device to know they are stimulating the right area, and other tests confirmed it. "I drank from a cup. I wrote my name. I drew a straight line," he says. (See a video of Mr. Miller that shows the device on and off.)

His device uses a battery pack on each side of his chest, which can be programmed separately. The tremors stop naturally while he's asleep, so he turns the DBS at night with a remote-control device.

"Once everything is turned on and working, you understand why you did this," says Mr. Miller, now 43, who is steady enough to work as a nurse's aide in a children's hospital. Some tasks, like typing and shaving, are still challenging. And like other DBS patients, he finds his emotions are heightened: "Some people laugh uncontrollably. Some people cry. A friend of mine with Parkinson's says he cries at railroad crossings."

All in all, he says, "It's not perfect, but it's pretty amazing. People with this condition should try it—they don't need to keep hiding."

* * *

ENLARGE

Paul and MaryAnn Kelley
Kelley family

Paul Kelley was only 30 when he was diagnosed with Parkinson's disease. He had to leave his job as a probation officer in Tallahassee, Fla., and take an administrative post because he couldn't carry a gun. By the time he decided on deep brain stimulation, at age 44, he couldn't work or operate a computer or walk.

A few days after the electrical current was switched on, he and his wife drove from the hospital in Gainesville to Disney World in Orlando. "I couldn't keep up with him, he was walking and talking so fast," recalls MaryAnn Kelley.

In fact, the settings on his battery pack were too high. It took several months of adjustments to get the speed and intensity just right. Much of Mr. Kelley's tremor and jerky movements are under control now, and he's been able to reduce his medication from 15 pills a day to four. The procedure has made his speech more difficult, however, and left him more emotional.

The Kelleys know that Paul's Parkinson's disease will continue to progress in the future. But for now, DBS "has given us our life back, in a lot of ways," says Mrs. Kelley. "He'll never be able to work again, but he coaches our son's baseball team. He plays golf. We go camping. We want to do as much as we possibly can as a family before we see the downside again. Next, we're going to go white-water rafting."

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